The lung contains enzymes which alter circulating substances in the blood, thereby influencing the composition of the systemic and bronchial circulations. These enzymatic alterations may be important in the regulation of peripheral vascular and bronchial muscle tone and in other physiological and biochemical activities of all tissues and organs. In addition, structural enzymes in the pulmonary circulation might be a source of circulating enzymes. Some of these enzymes may be located on endothelial cell surfaces. The objective of the proposed research is to obtain basic cellular and molecular information about the enzymatic processes in the pulmonary circulation. Angiotensin converting enzyme is an important structural enzyme in the lung which hydrolyzes angiotensin 1 to vasoactive angiotensin 2 and inactivates bradykinin by its dipeptidyl hydrolase activity. We have purified and studied this enzyme from rat lung. We plan to continue studies on the purification of this enzyme from various sources and on its physical, biochemical, and immunological properties. In particular, we wish to study the relationship of this enzyme in the lung to that in blood and in other tissues. We plan to obtain information about its localization in lung tissue by electron microscopic techniques utilizing antibody against converting enzyme conjugated to peroxidase. We hope to gain information about its site of synthesis and possible mode of release from the cell with the use of in vitro techniques and to determine if pulmonary disease processes result in alterations in converting enzyme in the lung or in the systemic circulation. We plan to extend these studies in a similar manner to other enzymes in the pulmonary circulation, including lipoprotein lipase, prostaglandin dehydrogenase, nucleotidase, and nucleoside and nucleotide deaminase, which may play important roles at the alveolar capillary interface.